title: Thioredoxin reductase was nitrated in the aging heart after myocardial ischemia/reperfusion.
abstract: The age-related loss of anti-oxidant defense reduces recovery from myocardial ischemia/reperfusion injury (MI/R) in aged people. Our previous data showed that inactivation of thioredoxin (Trx) was involved in enhanced aging MI/R injury. Thioredoxin reductase (TrxR), the enzyme known to regulate Trx, is less efficient with age. The aim of the current study was to determine why TrxR activity was reduced and whether reduced TrxR activity contributed to enhanced aging MI/R injury. Both Trx and TrxR activity were decreased in the aging heart, and this difference was further amplified after MI/R. However, MI/R injury did not change TrxR expression between young and aging rats. Increased nitrogen oxide (NOx) but decreased nitric oxide (NO) bioavailability (decreased phosphorylated vasodilator-stimulated phosphoprotein) was observed in aging hearts. Peroxynitrite (ONOO⁻) was increased in aging hearts and was further amplified after MI/R. TrxR nitration in young and aging hearts was detected by immunoprecipitation (anti-nitrotyrosine) followed by immunoblotting (anti-TrxR). Compared with young hearts, TrxR nitration was increased in the aging hearts, and this was further intensified after MI/R. The ONOO⁻ decomposition catalyst (FeTMPyp) reduced TrxR nitration and increased TrxR and Trx activity. More importantly, FeTMPyp attenuated the MI/R injury in aging hearts as evidenced by decreased caspase-3 and malondialdehyde (MDA) concentration and increased cardiac function. Increased ONOO⁻ nitrated TrxR in the aging heart as a post-translational modification, which may be related to the enhanced MI/R injury of aging rats. Interventions that inhibit nitration and restore TrxR activity might be a therapy for attenuating enhanced MI/R injury in aging heart.
authors.affiliation: 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University , Beijing, P.R. China .
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Zuo
authors.forename: Kehua
authors.initials: K
authors.lastname: Bai
authors.forename: Jianyu
authors.initials: J
authors.lastname: Shang
authors.forename: Lu
authors.initials: L
authors.lastname: Ma
authors.forename: Teng
authors.initials: T
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Xinliang
authors.initials: X
authors.lastname: Ma
authors.forename: Huirong
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D055162:Biocatalysis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology*; D015538:Nitrosation / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*
chemical_list: C492721:5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato-iron(III); D002316:Cardiotonic Agents; D008665:Metalloporphyrins; D030421:Peroxynitrous Acid; D013880:Thioredoxin-Disulfide Reductase